Pain Acupuncture_PMR Clinics

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The role of acupuncture in pain management

Joseph F. Audette, MA, MDa,b,*,Angela H. Ryan, MDa,b

aDepartment of Physical Medicine and Rehabilitation, Harvard Medical School,

Boston, MA, USAbSpaulding Rehabilitation Hospital, 125 Nashua Street, Boston, MA 02114, USA

Acupuncture has been used as a therapeutic modality for more than 3000

years, but it is only since the 1970s that a greater understanding of the

underlying mechanisms of acupuncture analgesia (AA) has developed. This

growth in understanding of AA has paralleled the scientific advances made

in uncovering the physiology of pain perception. Similar to many ancient

healing traditions, acupuncture has accumulated a wealth of anecdotalexperiences documenting its clinical effectiveness for a variety of problems.

Although acupuncture has survived the test of time, medicine today

demands more, and ultimately acupuncture must withstand the scrutiny

of science if it is to become a mainstay in the treatment of pain. Given the

explosion of interest within the scientific and clinical medical community in

acupuncture, it is fortunate that a substantial body of evidence to support

the efficacy of acupuncture exists, in contrast to many other complementary

and alternative medicine (CAM) therapies. This article outlines understand-

ing to date of the underlying physiologic mechanisms of AA, then reviewscurrent use of acupuncture in pain management for some common

musculoskeletal conditions seen in clinical practice.

Philosophy of acupuncture

Employed as one of many therapeutic interventions in Traditional

Chinese Medicine, acupuncture traditionally was believed to work by

maintaining and balancing the flow of Qiin the human body. Qiis a concept

that is difficult to translate into English, but it commonly is equated withvital energy and has been subsumed under the various Western traditions

* Corresponding author.

E-mail address: [email protected] (J.F. Audette).

1047-9651/04/$ - see front matter 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.pmr.2004.03.009

Phys Med Rehabil Clin N Am

15 (2004) 749772
mailto:[email protected]:[email protected]


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of vitalism. The concept of Qi is much more complex and broad reaching,

however, and interconnects living and inanimate objects in nature and the

universe. Qi is essentially an energetic concept that is postulated by Chinesephilosophy as a tangible force that allows energy transfer, movement,

growth, and development to occur. To maintain physical and mental health,

the flow of Qi must stay fluid and in balance macroscopically, as individuals

relate to their environment, and microscopically, as organ functions

interact. A blockage in the flow of Qi can cause an imbalance and eventually

manifest as disease.

According to Traditional Chinese Medicine, individuals can influence this

balance of Qi internally, by analyzing the flow of Qi along defined pathways

on the surface of the body in a set of channels called meridians (Fig. 1). Themeridians all are connected to each other and to all the internal organs in

complex patterns. Treatment involves first correctly identifying the internal

and external imbalances, then, by inserting needles into appropriate points

along the meridians, helping to realign Qi flow in the body to restore in-

ternal homeostasis [1,2].

Pain and analgesia

From a modern scientific perspective, the Chinese notion of Qi and

meridians has not been documented with current technologies. The basic

premise of acupuncture, in simplified terms, is that stimulation at one site on

the body has an effect on another, more distant site. Perhaps at a more

profound level, a second premise of acupuncture theory is that internal

pathology can be diagnosed and treated with surface evaluation and

Governing v.

Gall

bladder Pericardium

Urinary

bladder Heart Stomach Lung

Conception v. Liver 3 Warmers Kidney Small

intestine

Spleen Large

intestine

(

)

(

)14

13(

)

(

)12

11(

)

(

)10

9(

)

(

)8

7(

)

(

)6

5(

)

(

)4

3(

)

(

)2

1

Fig. 1. Acupuncture meridians.

750 J.F. Audette, A.H. Ryan / Phys Med Rehabil Clin N Am 15 (2004) 749772


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stimulation by taking advantage of somatovisceral and viscerosomatic

reflexes. The substantiation of these hypotheses has been made more

plausible with the growth in understanding of the neuroanatomy of painprocessing (discussed subsequently). First, the physiology of pain as it is

currently understood is outlined. Second, the evidence of how acupuncture

alters the transmission and perception of pain is presented. Finally, the

clinical evidence for the role of acupuncture in treating various pain

syndromes is reviewed.

Pain physiology

The physiology of pain perception and modulation is a sophisticated,

multilayered system that is activated with injury under normal circum-

stances. This activation leads to a complex series of events that includes

signal processing along neural pathways, immunologic and hormonal

releases, and psychobehavioral responses. The current thinking underlying

pain perception and inhibition accepts a dynamic, malleable, and complex

set of interacting neurons, with gene regulation and expression producing

a variety of neuropeptides and cytokines at the peripheral nervous system

and central nervous system (CNS) level. The recognition of the plasticity ofthe nervous system has revolutionized the understanding of pain, especially

chronic pain. After reviewing the neural pathways involved with pain

modulation, the authors explain how acupuncture is believed to influence

each of these domains.

Peripheral nervous system

The neuroanatomy of nociception can be organized into three distinct

but connected domains: the peripheral sensory apparatus, the spinal cord,and the brain. Starting in the periphery, small-fiber sensory axons that

respond to various types of noxious input are called nociceptors. There are

two main nerve types that carry pain and temperature informationthe

small, unmyelinated C fibers and the larger, thinly myelinated Ad fibers. In

the skin, the C fibers, which conduct more slowly than the Ad fibers and are

considered high-threshold nociceptors, carry more diffuse and dull pain

information and require higher levels of stimulation and tissue damage to

activate. The Ad fibers carry the sensation of sharp pain and are considered

low-threshold nociceptors, providing more discriminative information.Similar sensory afferents are found in muscle; however, in muscle, both

fiber types convey a dull aching sensation when activated, in contrast to skin

nociceptors (Fig. 2). In addition to nociceptors responding to mechanical

pain and temperature input, the release of chemical substances in tissues,

such as histamine, protons, bradykinin, vasoactive polypeptide, and a whole

array of others, can lead to nociceptor activation.

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Spinal cord

As with all afferent information, the sensory nerves from the skin enter

the dorsal side of the spinal cord. The cell bodies of these sensory nerves arein the dorsal route ganglion. When in the spinal cord, the fibers synapse in

laminae I through IV of the dorsal horn gray matter, with laminae I and II

receiving the bulk of the nociceptive input from the skin. Before entering the

dorsal horn, the primary sensory afferents branch and commonly ascend

and descend multiple segmental levels before ending in a synapse with

interneurons and second-order neurons. Most of the second-order neurons

cross the midline and travel to the brain on the contralateral side from the

site of nociception. Interneurons play a role in pain inhibition. The main

pathways involved are the spinothalamic and the spinoreticular tracts.Together, these tracts make up the anterolateral system of the CNS [3].

Brain

In the brain, multiple areas have been implicated as having some role in

pain perception and regulation. Spinal cord pathways synapse directly in the

Dorsal root

Ventrolateral

column

Descending

tracts

Skeletal muscle

Bare endings

Meissner's

corpuscles

Paciniancorpuscles

Musclespindle

Tendon

bundle

Anterior rootA-,

A-,A-, C

Fig. 2. Afferent sensory fibers enter the spinal cord via the dorsal root ganglion. Small, thinly

myelinated and unmyelinated fibers (Ad and C) enter the dorsal horn and distribute in the

lamina as indicated.



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brainstem reticular formation, the amygdala, the hypothalamus, and the

thalamus. At a higher level, the somatosensory cortex and higher cognitive

brain regions also are activated, although not directly [4]. These higher levelscontribute to the affective and emotional aspects of pain sensation. Research

has shown that stimulation of many nociceptors in the periphery are not

transmitted uniformly to the somatosensory cortex, but are transmitted to

other areas of the brain, such as the frontal cortex, subcortical areas in-

volved in the limbic system, and the hypothalamus [5].

Muscle pain physiology

The nociceptive information carried from muscles takes a slightlydifferent route than that carried from the skin. Outlining the different

pathways is important not only in understanding the experience of pain, but

also in understanding the possible neural mechanisms of acupuncture.

Acupuncture stimulation typically involves needle penetration to the muscle

and deeper connective tissue structures than the skin level. Similar to

nociceptive information from the skin, low-threshold and high-threshold

small fibers, named group III and IV fibers, travel to the dorsal horn of the

spinal tract and correspond to cutaneous Ad and C fibers, respectively.

These fibers synapse in the same lamina as cutaneous information, but havea higher representation in laminae IV and V. In laminae IV and V, wide

dynamic range (WDR) second-order neurons reside. In contrast to second-

order neurons in laminae I and II, which have an on-off response to sensory

input, WDR neurons have a graded response to sensory input. To illustrate,

normal stretch of a muscle stimulates low-frequency output of the WDR

neurons, which should not be perceived as painful, whereas high-frequency

input into the dorsal horn, such as after pathologic stretch and injury of

a muscle, causes high-frequency output and pain. Under pathologic con-

ditions, wind-up can occur in the second-order WDR neurons found inlaminae IV and V, and low-frequency input can lead to high-frequency out-

put. This heightened firing pattern of neurons in the CNS is believed to be

one of the factors involved with chronic pain [6]. Another unique feature of

WDR second-order neurons is that there is convergence of sensory

information from the afferents of skin, muscle, viscera, tendons, and joints

[7]. This convergence of sensory information opens the door to understand-

ing how sensory stimulation of muscles with acupuncture can influence

other visceral and somatic structures.

Chronic pain

Neuroplasticity of the peripheral nervous system and CNS lies behind

much of the current research and theory of chronic pain. Changes in

intracellular signal transduction, gene expression, receptor and ion channel

density, and depolarization thresholds contribute to a peripheral sensitization



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and central wind-up phenomenon in the pain pathway. Sensitization in the

periphery can occur directly at the small-fiber, nociceptor terminals by

repeated high-frequency stimulation or by the prolonged presence of signalingmolecules that signify damage or inflammation. These signaling mole-

cules include substance P, serotonin, bradykinin, epinephrine, adenosine, and

nerve growth factor, among others [8].

The changes in the dorsal horn of the spinal cord in response to persistent

nociceptive input invoke the wind-up phenomenon, as mentioned earlier.

Adopting the theory of long-term potentiation in the hippocampus as the

neuroplastic changes responsible for the learning and retention of new

information to form memories, a similar theory is hypothesized in the spinal

cord for the learning of chronic pain. Long-term potentiation representsa long-lasting change in neuronal synapses as a result of high-frequency

input. In the context of pain, nociceptive input from a prolonged noxious

stimulus may lead to neuroplastic changes in the spinal cord, which result in

a learned perception of pain, even when the noxious input is no longer

present. As discussed later, acupuncture may have a role in reversing some

of these neuroplastic changes.

Pain inhibition

At the peripheral and spinal cord level, the role of pain inhibition

originally was described via the gate control theory. Although the gate

control theory of pain as introduced by Melzack and Wall [9] in 1965 does

not fully explain pain inhibition, some of the segmental analgesic effects of

AA do invoke this system. It is a useful and applicable theory, especially

when it comes to understanding some of the theories of AA [10]. According

to the gate control theory, large, myelinated Ab sensory afferents synapse on

inhibitory interneurons in the dorsal horn, which when activated can inhibit

the activation of second-order neurons that receive input from the smallernociceptor fibers (Fig. 3).

Since the time of Melzack and Wall, theories of pain perception and

inhibition have focused more on a biochemical level involving gene

regulation, receptor expression, and depolarization thresholds. On the

peripheral level, central pathologic changes and peripheral injury can lead

to sensitization of the nociceptor terminal. Small-fiber, unmyelinated

afferents have been found to have retrograde, neurosecretory properties

similar to sympathetic fibers. Under pathologic conditions, substance P, a

neuropeptide that normally acts centrally, can be secreted peripherally atthe nociceptor terminal. This peripheral secretion of substance P can lead to

a cascade of events, including the degranulation of local mast cells, which

can cause a sensitizing chemical soup with molecules such as serotonin,

bradykinin, epinephrine, adenosine, and nerve growth factor (Fig. 4). This

process of peripheral sensitization has the consequence of lowering the

threshold by which the peripheral nociceptor fires in response to stimulation



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and can lead to the clinical phenomenon of hyperalgesia. In addition, it has

been found in animal models that acupuncture points have elevated levels of

substance P, suggesting a mechanism as to why needle stimulation at these

points may be activating sensitized peripheral nociceptors [11].

Dorsalhorn cell

Anticlromicstimulation

Nociceptor

Signal

Signal

CGRP

Blood vessel

NO,BradykininVasoactive

IntestinalPeptide

Edema

SerotoninHistamine

Mast cell

SubstanceP

Fig. 4. Diagram illustrates the neurosecretory actions of peripheral nociceptors and the role the

release of substance P plays in causing mast cell degranulation and peripheral sensitization.

CGRP, calcitonin generelated peptide; NO, nitric oxide.

Central control

To highercenters

Actionsystem

Gate-Control System

TSG

L

S

Inhibitory synapse

Excitatory synapse

Fig. 3. Gate control theory. (Modified from Mense S, Simons DG. Central pain and centrally

modified pain. In: Muscle pain: understanding its nature, diagnosis and treatment. Philadelphia:

Lippincott Williams & Wilkins; 2001. p. 176; with permission.)



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At the level of the spinal cord, the interneurons, which receive nociceptive

and non-nociceptive afferent information, act on WDR and other second-

order neurons to alter pain perception. Presynaptic inhibition, which acts tohyperpolarize presynaptic pathways and reduce their activation of pain

tracts, is often mediated by c-aminobutyric acid. Interneurons also act

postsynaptically by inhibiting signal transmission to second-order neurons.

Postsynaptic inhibition is mediated primarily by opioids and glycine. It is

also at the postsynaptic level that supraspinal signals from the descending

pathways exert their influence. These signals are mediated by, among other

things, norepinephrine, serotonin, and acetylcholine [12].

Inhibition of pain at the level of the brain has come to be understood well

through the role of endogenous opioids and the descending pain inhibitorysystem. Endogenous opioids, such as endorphins, dynorphins, and enke-

phalins, are peptides that act in the CNS to modulate pain. There are a few

well-identified areas of the brain and spinal cord that are known to be sites

of opioid action: the hypothalamus, limbic system, basal ganglia and

periaqueductal gray area, nucleus raphe magnus, reticular activating system,

and spinal cord in the dorsal horn. The descending inhibitory system travels

from the hypothalamus and periaqueductal gray, through the medulla

(where the nucleus raphe magnus and reticular activating system are) to the

dorsal horn of the spinal cord, where inhibition of the afferent nociceptiveinformation occurs (Fig. 5). As discussed later, acupuncture research has

shown that it has a role in activating this descending inhibitory system.

Mechanism of acupuncture analgesia

Acupuncture and the peripheral nervous system

It has been possible to explain some of the Traditional Chinese Medicine

experiences of acupuncture, such as the sensation of De Qiand the meridiansystem, by more modern understanding of anatomy and physiology.

Traditionally, Chinese acupuncture needle manipulation at specified points

is verified to be accurate when the recipient experiences a De Qi sensation,

which is described as a deep aching sensation. It now is believed that this

sensation is a sign of the activation of group III and IV fibers in skeletal

muscle. An analogy has been drawn in tying the physiologic benefits of

sustained physical exercise and the stimulation of the same muscle afferents

that are activated with acupuncture stimulation [13]. As mentioned earlier,

the distribution of these muscle sensory afferents to the dorsal horn of thespinal cord may play an important role in the observed physiologic effect of

acupuncture stimulation, especially if these afferents are sensitized, as

evidenced by elevated substance P found in animal models of acupuncture

points.

Additionally the correlation between acupuncture points and myofascial

trigger points has been mapped [14]. Keeping in mind the differences in



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muscle and skin pain pathways previously outlined, stimulation of muscle

tissue (as in trigger point injections and acupuncture) not only may have

a pain-inhibitory effect, but also may influence visceral structures and

remote somatic structures because of sensory convergence on the same

WDR second-order neurons.

Acupuncture and descending pain inhibition

The most well-delineated effect that acupuncture has on pain inhibition isthe way it influences the descending inhibitory pain system. In the late 1970s

and early 1980s, many studies investigated the relationship between

acupuncture and pain inhibition. The studies measured either opioid activity

in the brain in relationship to AA or a reduction in AA with the

administration of opioid antagonists, such as naloxone or naltrexone, and

compared the analgesic effects of acupuncture with those of morphine.

Nociceptive input

NRM

From hypothalamusTo thalamus

PAG

Rostral

medulla

Spinalcord

NE 5-HT SP?

GABA?

EAA/NT?

Enkephalinergic neuron

Inhibitory synapse

Excitatory synapse

Fig. 5. The descending pain modulation system. The periaqueductal gray area (PAG) is in the

mesencephalon and is a major control area for the descending system. The rostral medulla level

is where the nucleus raphe magnus (NRM) and the reticular activating system (RAS) are

located and is where multiple descending antinociceptives tracks originate. Cells in these centers

are activated by excitatory amino acids (EAA), such as glutamate and aspartate and possibly

neurotensin (NT). From here, the descending tracks enter the dorsal horn of the spinal cord,

and inhibition is mediated mainly by norepinephrine (NE) and serotonin (5-hydroxytryptamine

[5-HT]). (Modified from Mense S, Simons DG. Central pain and centrally modified pain. In:

Muscle pain: understanding its nature, diagnosis and treatment. Philadelphia: Lippincott

Williams & Wilkins; 2001. p. 177; with permission.)



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Acupuncture has been shown to influence pain perception by modulating

the activity of key subcortical and brainstem sites along the descending pain

modulating system pathway [15].Given the variety of neurotransmitters discussed so far involved in the

peripheral sensitizing soup and the wind-up phenomenon, it is not

surprising that there are potentially many nonopioid mechanisms of

analgesia that may be involved. As just one example, low-intensity and

high-frequency electrical stimulation has a faster onset of action but does

not have as prolonged an effect as high-intensity and low-frequency

stimulation. The former is thought to be serotoninergic mediated and the

latter opioid mediated [16].

Although the demonstration that endogenous opioids and other neuro-transmitters can be released consistently in animal and human experimental

models has been an important step in verifying that AA has a physiologic

basis, there continues to be debate about whether this effect is sufficient to

explain the observed clinical benefits. One of the problems is that such

humoral effects are nonspecific and short-lived and cannot explain why

certain treatment methods for particular conditions would have a sustained

or permanent disease-modifying result. The chemical releases observed with

electroacupuncture (EA) and manual acupuncture (AP) may just be an

epiphenomenon, indicating that there has been an influence on the CNSwithout fully comprehending what the actual homeostatic influence has

been.

One theory that may help to explain better the long-term effect of EA and

AP is that by stimulating peripheral sensory afferents of the skin and muscle,

sustained changes occur in the CNS via central neuromodulation. A

fundamental concept that has emerged is that sustained nociceptive input

can have profound effects on the CNS causing pathologic neuroplastic

changes. Continuing along this line of argument, in contrast to trans-

cutaneous electrical nerve stimulation (TENS), AP and EA do rely ona more painful stimulation of the peripheral nervous system. In effect,

through controlled stimulation of peripheral nociceptors, acupuncture may

be causing a reverse neuroplasticity in the CNS.

A clue to the neuroplastic changes that may be occurring in the CNS with

EP and AP can be found in the literature looking at c-Fos expression. The

expression of the gene c-Fos in the CNS occurs in cells believed to be

activated after noxious peripheral stimulation. The Fos protein is the

nuclear product of the immediate-early gene c-Fos and couples transient

intracellular signals to long-term changes in gene expression and is believedto herald neuroplastic changes in the CNS [17]. A body of literature has

looked at c-Fos expression in the spinal cord and brain in relation to

acupuncture. Acupuncture has been shown to suppress c-Fos expression in

the spinal cord and the brain after noxious peripheral stimulation,

suggesting a possible neuromodulatory mechanism that is independent of

endogenous opioid release [18].



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Acupuncture and the brain

The advent of functional MRI has provided an intriguing method to look

into the effect that acupuncture has on brain activation. These studies give

some of the strongest evidence for acupuncture point specificity and help to

argue against critics who argue that AA is due to nonspecific, inhibitory

control mechanisms induced by the noxious needle stimulation. This

evidence for point specificity was shown elegantly by Cho et al [19]. An

acupuncture point on the lateral aspect of the small toe, Bladder 67 (B67),

which in some acupuncture systems is believed to be an influential point for

vision, was stimulated and observed to cause increased functional MRI

activity in the occipital lobes in 12 subjects. Stimulation of the eyes directly

with light caused a similar activation, whereas stimulation of a sham

acupuncture point 2 to 5 cm away from B67 failed to cause occipital lobe

activation [19]. In another study, comparison has been made between tactile

sensation (tapping the skin with a wire at 2 Hz) versus AP using a classic

Chinese manual stimulation technique in which the needle is twisted at 2 Hz

in LI4 (a point in the first dorsal interosseous muscle of the hand).

Stimulation of an acupuncture point in this manner produces a De Qi

sensation, which is a full, aching feeling at the point of the needle and is

believed by some to be important in obtaining the clinical effect with AP.

The results of unilateral AP showed bilateral neural modulation of cortical

and subcortical structures. The primary action was to decrease signal

intensity in the limbic region and other subcortical areas. Tactile stimulation

did not produce these changes in functional MRI. This finding suggests

a differential response of the organism to AP depending on whether there is

activation of the muscle sensory afferents versus the superficial afferents in

the skin [20].

Acupuncture and placebo mechanisms

Similar to many CAM interventions, the effects of acupuncture some-

times are attributed to the placebo effect. Some authors theorize that

placebo is an endorphin-mediated effect, making acupuncture a particularly

powerful form of placebo [21]. The ritual of CAM interventions may lend

themselves to causing an enhanced placebo effect, which can have powerful

therapeutic implications [22]. Acupuncture has the advantage of activating

reproducible biologic mechanisms, while bringing to the therapeutic

encounter some of the attributes of a psychological interaction, such as

longer patient-healer time together and the power of touch and suggestion.Nevertheless, in an attempt to validate the scientific efficacy of acupuncture,

the trend is to eliminate from the traditional therapeutic model the elements

that may have a profound effect on the efficacy of the intervention. Great

emphasis has been placed on identifying appropriate sham acupuncture

controls and taking into account things such as patient expectation of

success before treatment. Time will tell whether acupuncture and many



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other CAM interventions will survive the scientific constraints imposed on

them.

Acupuncture in the clinical setting

In the early 1990s, by an act of Congress, the National Institutes of

Health (NIH) formed an Office of Alternative Medicine, which subsequently

became the National Center for Complementary and Alternative Medicine

in 1998. The main objective of the center was to fund basic and clinical

research in various CAM therapies with the ultimate goal of providing

clinicians evidence to guide care. The first NIH-sponsored event for

acupuncture was the 1994 Workshop on Acupuncture, which resultedin the Food and Drug Administration changing the status of acupuncture

needles from experimental to a nonexperimental but regulated medical

device status. In 1997, the NIH held its first consensus conference in

acupuncture and published a guideline to clinicians summarizing the

evidence to date on the use and effectiveness of acupuncture in a variety

of medical conditions [23]. In the realm of pain conditions, the panel

concluded that the literature showed acupuncture is effective in treating

postoperative dental pain. The panel also concluded that acupuncture may

be useful in treating headache, menstrual cramps, tennis elbow, fibromyal-gia, myofascial pain, osteoarthritis, low back pain, and carpal tunnel

syndrome. This statement was based on an exhaustive review of the

literature, much of which can be characterized by poorly powered studies

of marginal experimental design. As a result of the paucity of quality studies

reviewed, the NIH consensus statement often relied on only a single study

for any given pain syndrome, and as a result, a strong endorsement could

not be made.

Acupuncture in clinical research

One of the issues that should be addressed in reviewing the acupuncture

literature is the methodologic problems faced by CAM researchers in their

attempts to apply reductionist, scientific paradigms to clinical methods

whose efficacy may depend on the interplay of a variety of nonreducible

factors. The practice of acupuncture is practitioner dependent, making it

hard to compare studies given the variety of techniques and treatment

paradigms used in different clinical settings (Fig. 6). Often care also includes

dietary recommendations, soft tissue and manipulative techniques, and attimes recommendations for herbal combinations. In contrast, a standard

research design, in an attempt to eliminate bias and maintain reproducibil-

ity, may reduce this robust acupuncture treatment paradigm to a fixed set of

points, potentially robbing the treatment of its efficacy.

Another common problem for nonpharmacologic clinical studies due to

underfunding is the issue of small sample size, leaving the study un-



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derpowered to draw valid conclusions. This is a particular problem when the

study design includes use of a powerful placebo stimulus, such as sham

needle stimulation of points on the body considered to be off meridian.

Sham needling, which involves the insertion of an acupuncture needle into

the tissue of a subject on a point off meridian and manipulating the needle as

one would at an actual point, often has a strong, nonspecific, physiologic

effect. As a result, large numbers of subjects would be required todistinguish the main effect of true point stimulation compared with this

type of aggressive placebo needling and avoid a type 2 error or rejection of

the null hypothesis. Other placebo needling methods are noninvasive, but

there is much debate in the scientific community about the validity of such

devices (Fig. 7). It is impossible to blind the practitioner and difficult to

blind the subjects in controlled trials, often necessitating the recruitment of

acupuncture-naive subjects. This being said, the number of clinical studies

evaluating the efficacy of acupuncture for treating various pain syndromes

has continued to increase, with studies of better quality being published inthe past few years, which are reviewed here.

Spine-related disorders

Of all the pain-related conditions, back pain is the most frequently

studied with acupuncture as an intervention. Meta-analyses of randomized

Fig. 6. Korean hand acupuncture montage illustrates the variety of clinical methods used in the

United States and around the world. This is a microsystem commonly used by Korean

acupuncturists. Often these points would not be needled, but rather heated by burning

a combustible herb, mugwort. This technique of heating points by burning mugwort is calledmoxibustion.



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controlled trials using acupuncture for back pain conclude that acupuncture

has been shown to be superior to various control interventions, but not

enough data are currently available to support its efficacy over sham

acupuncture needling [24,25].

In a prospective, randomized controlled trial, 186 subjects with chroniclow back pain were recruited, 124 of whom completed the full treatment and

follow-up protocol. Subjects were randomized to three groups: acupuncture

with conservative orthopedic treatment, sham acupuncture with conserva-

tive orthopedic treatment, and conservative orthopedic treatment alone.

Subjects in the verum (or true acupuncture) and sham acupuncture groups

received 12 treatments while undergoing spine rehabilitation for conserva-

tive orthopedic treatment. Significant improvement in visual analogue scale

pain scores in the acupuncture group was found at the end of treatment and

at a 3-month follow-up compared with the sham and conservativeorthopedic treatment groups [26].

In 1999, the Journal of the American Medical Association published a well-

designed randomized crossover study comparing percutaneous electrical

nerve stimulation (PENS) versus TENS versus sham PENS versus exercise.

The study included 60 patients with low back pain secondary to de-

generative joint disease. Each patient had 3 weeks of each treatment three

times a week with a 1-week break in between treatment types. The PENS

treatment showed significant improvements in pain scores, function, and

reduced use of analgesics compared with the control groups [27]. PENS issimilar to acupuncture in that it involves the insertion and subsequent

electrical stimulation of acupuncture-type needles into the deep tissue and

muscles. Needle placement is not motivated by acupuncture theory, howeve;

rather needles are placed to surround the dermatomal and myotomal

distribution of the patients pain condition (Fig. 8). Some methodologic

problems with the study include concerns about the validity of using TENS

1

23

4

5 1

23 4

512 4

5

6

78

9

1 Needle handle2 Needle3 Blunt tip of the placebo needle4 Plastic ring5 Plastic cover

6 Skin7 Dermis8 Muscle9 Sharp tip of acupuncture needle

Fig. 7. The placebo needle. (From Kleinhenz J, Streitberger K, et al. Randomized clinical trial

comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff

tendinitis. Pain 1999;83:23541; with permission.)



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as a placebo control for needle stimulation. In addition, the exercise

protocol used was oversimplified, and long-term outcomes were not studied.

A randomized trial compared acupuncture with massage therapy and

self-education for treatment of chronic low back pain. The sample size was

large; the participants were evaluated 1 year after treatment, which was 10

weeks long; and multiple providers were used. The study concluded massagetherapy to be superior to acupuncture and self-education at the end of the 10

weeks and at 1-year follow-up [28]. The positive effect of acupuncture was

concentrated in the first 4 weeks of treatment. Many factors could account

for the less favorable outcome of the acupuncture group, including point

selection, limited treatment sessions, and, most importantly, the fact that

the acupuncturists felt constrained by the study protocol in treating their

patients in most cases. This last factor speaks to the issue that the acu-

puncturists who agreed to participate in the study were not permitted to

go beyond needling in their treatment protocol, limiting them from usingvarious massage and nutritional methods that they normally would in-

corporate into their care.

There are far fewer well-designed studies looking at acupuncture for neck

pain. A review published by White and Ernst [29] found that most of the

studies failed to satisfy methodologic quality standards. When they looked

specifically at the eight methodologically most rigorous studies, they found

+

+

+

+

+

12

L5

S1S

2S3

L4L3L2L1

T12

Fig. 8. Percutaneous electrical nerve stimulation montage for low back pain following

a dermatomal distribution of pain. Plus and minus circles represent the application of positive

and negative electodes from an electro-acupuncture stimulator to the inserted needles. Needlesare inserted through the cutaneous layer into deep muscle tissue.



16/24

that five of them had results that did not support acupuncture for the

treatment of neck pain. The most rigorous studies inevitably included a sham

needling control group or other interventions with strong, nonspecifictherapeutic effects. The review supported the conclusion that acupuncture is

superior to a waiting-list control, but it is unclear if it is equivalent or

superior to physical therapy.

In another randomized controlled trial, designed specifically to correct

some of the weaker points of previous trials, including recruitment of

a larger sample size, use of blinded outcome observers, and use of blinded

patients for a placebo control using sham acupuncture points. Subjects

(n = 177) were randomized to acupuncture versus massage versus sham

acupuncture. Each treatment group received five treatments over 3 weeks.The investigators concluded that acupuncture was more effective than

massage, but not more effective than the sham acupuncture points in

decreasing pain with motion. They also found that the patients who had

greater than 5 years of pain and patients with myofascial pain did the best

with acupuncture [30]. A reanalysis of the data using a linear regression

model supported the fact that acupuncture was more effective in reducing

pain than sham acupuncture [31]. The support for acupuncture as

a treatment modality for chronic neck pain shows some promise given this

well-designed study.

Arthritis

One of the most thorough and more recent systematic reviews looked

exclusively at acupuncture for the treatment of osteoarthritis of the knee.

The strength of the review is that it rated seven different clinical trials

on the basis of whether or not the acupuncture treatment they used

conformed to guidelines and recommendations put forth by many

acupuncture experts. These guidelines included (1) an average of 10treatment sessions for a chronic condition, (2) stimulation of at least

eight points per session, (3) elicitation of the De Qi sensation, and (4) use

of a combination of high-frequency and low-frequency stimulation when

EA is used to avoid accommodation to the electrical stimulation. The

review also rated studies on the quality of their design and the type of

control group they used. Four of the seven studies found acupuncture to

have a positive effect on pain, and three of the studies were neutral. No

studies reported acupuncture as having a negative effect on pain associated

with knee osteoarthritis. Three high-quality studies compared real acu-puncture with sham acupuncture, and two of them reported positive

results. None of the trials conformed to all four of the guidelines deemed

necessary by the acupuncture experts for adequate acupuncture treatment.

The most important guideline is treatment duration for a chronic

condition, such as osteoarthritis of the knee. The three studies that

administered the minimum of 10 treatments all had positive results [32].



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One study, although it did not include a sham control group, did show an

improvement in subjective pain and functional scores in a group of

osteoarthritis patients who underwent acupuncture. One of the strengthsof this study was the frequency of the intervention: The subjects completed

biweekly acupuncture treatments for 8 weeks. The positive effect of

acupuncture was sustained 12 weeks after treatment. However, The benefit,

although it remained significant, decreased at this 12-week point, suggesting

that maintenance therapy may be beneficial [33]. Future studies should

compare the cost and health risks of sustained use of ongoing oral analgesics

for osteoarthritis of the knee versus intermittent acupuncture treatments to

maintain pain relief and function. To give an example of the possible cost

savings, in one study of severe osteoarthritis of the knee in which thepatients enrolled were on a waiting list for total knee replacement,

Christensen et al [34] found a significant reduction in pain and use of

analgesic medications compared with a control group. This benefit was

sustained, and 7 of 29 patients enrolled declined the total knee replacement

operation at the end of the wait, saving $9000 per patient.

The literature on acupuncture for the treatment of rheumatoid arthritis is

sparse. A Cochrane systematic review identified only two studies that met

methodologic standards for inclusion. One study compared acupuncture

with placebo and found no difference in pain after 5 weeks of treatment. Thesecond study compared EA with placebo and found a significant decrease in

knee pain after 24 hours, but not at 1 month, 2 months, or 3 months after

treatment. The treatment protocols in both trials normally would not be

deemed of sufficient length by acupuncture standards to have a sustained

effect on such a chronic condition as rheumatoid arthritis of the knee. These

studies of short treatment duration do not support the use of acupuncture in

rheumatoid arthritis patients, but they lay the groundwork for future

research [35].

Fibromyalgia

Compared with spine-related disorders and arthritis, there is a paucity of

studies looking at acupuncture for the treatment of fibromyalgia and other

soft tissue pain conditions. A review found only three randomized controlled

trials that fit their inclusion criteria [36]. Only one of the studies in the review

was considered to be of high methodologic quality. In that study, 70 patients

were randomized into sham and treatment groups. They each received six

sessions of either verum or sham acupuncture over 3 weeks and subsequentlywere evaluated independently by a blinded physician. The treatment group

had a 70% decrease in pain compared with the control group, which had only

a 4% decrease. The treatment group also reported less morning stiffness and

better global improvement ratings by the patient and the physician [37]. In

another randomized controlled trial, verum and sham acupuncture groups

were randomized with and without amitriptyline (25 mg) in 60 subjects with



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fibromyalgia. Treatment was provided for 16 weeks with assessments at 4, 8,

12, and 16 weeks by a blinded investigator. The verum acupuncture group

showed significant improvement in pain and mood compared with the shamgroup and amitriptyline-alone group [38]. These results may suggest that

a chronic pain problem, such as fibromyalgia, that theoretically may result

from abnormal central neuroplastic changes may respond better to acupunc-

ture than would a pain condition such as rheumatoid arthritis of the knee,

which involves severe structural damage to a joint.

Myofascial pain

Myofascial pain syndrome frequently involves the supporting posturalmusculature of the spine and extremities and likely contributes to the pain

seen in many of the spine studies already reviewed [39,40]. One widely

accepted mechanism for the treatment of myofascial pain is hyperstimula-

tion analgesia by stimulating the trigger points via dry needling, intense cold

or heat, or chemical stimulation to the skin. The success of these techniques

in the past has been ascribed to the gate control theory of pain [41].

Acupuncture needling potentially could be an additional method of

hyperstimulation and might be expected to be a viable treatment for

myofascial pain. Additionally, when examining the acupuncture literaturefrom the Tang Dynasty (AD 581-682), one finds that Sun Si-Miao developed

the theory ofAh Shipoints. This theory states that whenever there is a local

soreness or pressure, there is an active acupuncture point regardless of

whether or not the point lies on a classic acupuncture meridian. Many

acupuncturists routinely needle such points in therapy, effectively treating

many trigger points by dry needling similarly to their allopathic colleagues

(Table 1); this complicates the whole notion of sham acupuncture needling

off meridian in controlled studies because the Ah Shi point needling is

standard practice among acupuncturists when not constrained to a researchprotocol for the treatment of various pain problems.

Nabeta and Kawakita [42] compared acupuncture with sham acupunc-

ture on tender points (Ah Shi points) in volunteers with complaints of

chronic pain and stiffness in the neck and shoulder. They treated Ah Shi

points once a week for 3 weeks. They found that there was a short-term

improvement using verum acupuncture, but they did not show a long term

superiority of verum over sham acupuncture. Irnich et al [43] published

a randomized double-blinded, sham-controlled, crossover trial comparing

dry needling and acupuncture at distant points for chronic neck pain. Eachtreatment was performed only once. Verum acupuncture was found to be

superior to sham acupuncture in improving motion-related pain and

improving range of motion, and acupuncture at distant points improved

range of motion more than dry needling. Kung et al [44] evaluated

a meridian-based treatment protocol for chronic myofascial pain in the

cervical and upper back regions and found short-term, but not long-term,



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pain relief. The study limited treatment to 3 weeks with two sessions each

week. All of these trials found acupuncture to be effective in the short-term,

with diminishing effects over time. All of these trials used extremelyabbreviated treatment protocols, however, potentially influencing the

long-term outcome.

Tendinitis

Tendinitis is a common problem among athletes and in the workplace,

with repetitive injuries to the upper extremities. Lateral elbow pain, or

lateral epicondylitis, has been treated by acupuncture in China for many

years. A Cochrane systematic review compiled in November 2001 reviewedthe literature and determined that only four randomized controlled trials

met their methodologic search standards. Of the four, two showed a positive

effect [45]. In one study, acupuncture improved pain scores after one session,

an effect that lasted for approximately 20 hours. A total of 48 patients

entered the study and received one session of needling of a point on the leg,

Gallbladder 34 (a point influential for tendinomuscular problems), versus

Table 1

Acupuncture and myofascial trigger point correlations

Acu-zone Region of body Acu-points MusclesTai Yang Dorsal zone: B 2-B 7 Frontalis

Frontal region

of forehead to

occiput down

back to lateral

ankles

B 10 Sub occipital

SI 9-14 Scapular

B 11-25, 41-45 Thoracic and lumbar paraspinals

B 53, 54 Gluteus medius

B 31, 34 Piriformis

Shao Yang Lateral zone: GB 3-6, 8 Temporalis

Temporalis

region of head

to lateral neck

and down arm

to wrist

extensors.

Down flank to

lateral aspect

of leg

GB 16 Sternocleidomastoid and scalenes

GB 20, 21 Upper trapezius

TH 9 Finger extensors

GB 24-28 Abdominal obliques

GB 29 Tensor fasciae latae

GB 31 Iliotibial band

Yang Ming Ventral zone: ST 5-7 Masseter

Mouth to

anterior neck,

anterior chest

wall down

abdomen to

medial aspect

of leg and

foot

ST 9, 10 Sternocleidomastoid

ST 14-18 Pectoral muscles

ST 19-30 Rectus abdominis

ST 31, 32 Quadriceps

Abbreviations: B, urinary bladder; GB, gallbladder; SI, small intestine; ST, stomach; TH,

triple heater.



20/24

sham needling of an unrelated point. In the treated group, the pain scores

decreased 55.8% compared with the sham control, which had a 15%

reduction in pain level [46]. Another study, done after the Cochrane reviewwas published, looked at acupuncture versus sham needling at adjacent

nonacupuncture points for lateral epicondylitis. The study design random-

ized 45 patients into the sham and verum acupuncture groups, and each

subject received 10 sessions of acupuncture over 5 weeks. The acupuncture

group did significantly better than the sham group in all measures at 2

weeks. At 2 months, arm function was better in the acupuncture group, but

measures of pain intensity or strength were not significantly different from

the sham group [47].

A randomized controlled trial using acupuncture for rotator cufftendinitis offered some positive results. After eight acupuncture sessions

provided in a 4-week period, subjects showed significant improvement in

pain and function compared with the placebo control group [48]. An

important methodologic aspect to this study was that the placebo control

was a specially designed needle that replicated visually and tactilely the

insertion of a real acupuncture needle (Fig. 7).

Neurologic disorders

Although acupuncture in the studies available to date has not proved aseffective for progressive neurologic disorders, such as human immunodefi-

ciency virus neuropathy, studies have supported its efficacy in the treatment

of carpal tunnel syndrome. A randomized controlled trial with a crossover

design of 11 patients compared laser acupuncture and microamperage

TENS stimulation versus sham laser acupuncture. Each group had 9 to 12

treatments over a 3- to 4-week period, then they were crossed over. There

was a significant decrease in pain and improvement in the sensory latency as

measured by nerve conduction studies 1 week after treatment [49]. Although

there were only 11 subjects, the results are promising and provide a goodfoundation for future studies looking at acupuncture in carpal tunnel

syndrome. Although the use of laser acupuncture is still controversial

because of the lack of needle penetration to effect the treatment, this

approach has the benefit of being more easily blinded. Because one cannot

feel a cold laser, and the light spectrum applied is in the infrared wavelength,

the subject and the practitioner can be blinded, making the results from the

Naeser study even more impressive [50]. Another study found that cold laser

stimulation of UB 67 in the foot (the same point used by Cho et al [19] with

needles) activated the visual cortex when imaged by functional MRI,substantiating the physiologic effect of laser acupunture [51].

Other pain disorders found in a rehabilitation setting

A review of the literature for using acupuncture to treat other pain

disorders, such as pain associated with spinal cord injury, stroke, and



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phantom limb, reveals a sparse number of isolated and often poorly

designed studies. Although acupuncture is used for these disorders and

may be beneficial, currently there are few studies to draw any sort ofclinically applicable conclusions.

Summary

Recent years have shown an increase in the quality of trials examining the

clinical efficacy of acupuncture for back and neck pain, arthritis, carpal

tunnel syndrome, fibromyalgia, and upper extremity tendinitis. Randomi-

zation, appropriate sample size, and blinding using more sophisticated shamprocedures raise the quality of the studies from a scientific, methodologic

point of view. In addition, realistic treatment frequency and duration of

some of the more recent studies have resulted in more favorable outcomes.

Much work still has to be done, however, to find ways to preserve the

clinical authenticity of acupuncture treatment methods when brought into

the light of a research protocol. Attempts have been made to find a method

of maintaining the standardization and reproducibility of a research pro-

tocol, while allowing the kind of flexible treatment that normally would be

applied in a clinical setting [52,53].Other questions that should be answered with future studies include

understanding how treatment length influences outcome, if maintenance

treatments are needed for chronic conditions, and cost and risk comparisons

with standard pharmacologic treatment. In addition, future studies need

more overt statements of the rationale for the treatment method used (eg,

were Chinese or Japanese diagnostic methods used for point selection, what

needling technique was used, was the De Qi sensation elicited) [54]. If an EA

protocol is used, details of the frequency and intensity parameters are

needed. Providing this kind of detail assists with reproducibility and helpsclinicians gain a better understanding about whether certain treatment

paradigms are superior to others for specific clinical conditions. Finally,

physicians who have an interest in pursuing acupuncture research should

educate themselves about the methodologic issues inherent with acupunc-

ture research and about authentic acupuncture treatment protocols so that

the literature is not populated with more poorly designed studies.

With the emerging interest in integrative medicine, there is a growing

interest in collaboration and a greater number of physicians interested in

obtaining training in acupuncture to help bridge this gap between CAM andconventional clinicians. The American Academy of Medical Acupuncturists

(AAMA) has been formed to help as an educational and research forum for

physician acupuncturists. Currently, physicians are able to satisfy the

educational and clinical requirements demanded by most states by com-

pleting the training offered by the Office of Continuing Medical Education

at the University of California Los Angeles. Harvard Medical School,



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through the Department of Physical Medicine and Rehabilitation and the

Department of Anesthesiology and Critical Care at Beth Israel Deaconess

Medical Center, also now offers a 300-hour continuing medical educationcourse in medical acupuncture that satisfies the AAMA requirements and

most hospital and state requirements to practice acupuncture. The Harvard

course also gives graduates a detailed understanding of the methodologic

issues involved with scientific research in this field. In time, with more highly

trained physicians, the future of acupuncture research should be secure,

allowing clinicians to understand better the role of acupuncture in the

treatment of pain disorders.

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